AT1 and glutamatergic receptors in paraventricular nucleus support blood pressure during water deprivation

Korrina L. Freeman, Virginia Brooks

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Water deprivation activates sympathoexcitatory neurons in the paraventricular nucleus (PVN); however, the neurotransmitters that mediate this activation are unknown. To test the hypothesis that ANG II and glutamate are involved, effects on blood pressure (BP) of bilateral PVN microinjections of ANG II type 1 receptor (AT1R) antagonists, candesartan and valsartan, or the ionotropic glutamate receptor antagonist, kynurenate, were determined in urethane-anesthetized water-deprived and water-replete male rats. Because PVN may activate sympathetic neurons via the rostral ventrolateral medulla (RVLM) and because PVN disinhibition increases sympathetic activity in part via increased drive of AT1R in the RVLM, candesartan was also bilaterally microinjected into the RVLM. Total blockade of the PVN with bilateral microinjections of muscimol, a GABAA agonist, decreased BP more (P <0.05) in water-deprived (-29 ± 8 mmHg) than in water-replete (-7 ± 2 mmHg) rats, verifying that the PVN is required for BP maintenance during water deprivation. PVN candesartan slowly lowered BP by 7 ± 1 mmHg (P <0.05). In water-replete rats, however, candesartan did not alter BP (1 ± 1 mmHg). Valsartan also produced a slowly developing decrease in arterial pressure (-6 ± 1 mmHg; P <0.05) in water-deprived but not in water-replete (-1 ± 1 mmHg) rats. In water-deprived rats, PVN kynurenate rapidly decreased BP (-19 ± 3 mmHg), and the response was greater (P <0.05) than in water-replete rats (-4 ± 1 mmHg). Finally, as in PVN, candesartan in RVLM slowly decreased BP in water-deprived (-8 ± 1 mmHg; P <0.05) but not in water-replete (-3 ± 1 mmHg) rats. These data suggest that activation of AT1 and glutamate receptors in PVN, as well as of AT1R in RVLM, contributes to BP maintenance during water deprivation.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume292
Issue number4
DOIs
StatePublished - Apr 2007

Fingerprint

Water Deprivation
Paraventricular Hypothalamic Nucleus
Blood Pressure
Water
Valsartan
Kynurenic Acid
Microinjections
Maintenance
GABA-A Receptor Agonists
Ionotropic Glutamate Receptors
Neurons
Excitatory Amino Acid Antagonists
Muscimol
Urethane
Glutamate Receptors
Neurotransmitter Agents
Glutamic Acid
Arterial Pressure

Keywords

  • Angiotensin II
  • Candesartan
  • Glutamate
  • Rostral ventrolateral medulla
  • Valsartan

ASJC Scopus subject areas

  • Physiology

Cite this

@article{0148b445e9ed430998872ff5f788fb41,
title = "AT1 and glutamatergic receptors in paraventricular nucleus support blood pressure during water deprivation",
abstract = "Water deprivation activates sympathoexcitatory neurons in the paraventricular nucleus (PVN); however, the neurotransmitters that mediate this activation are unknown. To test the hypothesis that ANG II and glutamate are involved, effects on blood pressure (BP) of bilateral PVN microinjections of ANG II type 1 receptor (AT1R) antagonists, candesartan and valsartan, or the ionotropic glutamate receptor antagonist, kynurenate, were determined in urethane-anesthetized water-deprived and water-replete male rats. Because PVN may activate sympathetic neurons via the rostral ventrolateral medulla (RVLM) and because PVN disinhibition increases sympathetic activity in part via increased drive of AT1R in the RVLM, candesartan was also bilaterally microinjected into the RVLM. Total blockade of the PVN with bilateral microinjections of muscimol, a GABAA agonist, decreased BP more (P <0.05) in water-deprived (-29 ± 8 mmHg) than in water-replete (-7 ± 2 mmHg) rats, verifying that the PVN is required for BP maintenance during water deprivation. PVN candesartan slowly lowered BP by 7 ± 1 mmHg (P <0.05). In water-replete rats, however, candesartan did not alter BP (1 ± 1 mmHg). Valsartan also produced a slowly developing decrease in arterial pressure (-6 ± 1 mmHg; P <0.05) in water-deprived but not in water-replete (-1 ± 1 mmHg) rats. In water-deprived rats, PVN kynurenate rapidly decreased BP (-19 ± 3 mmHg), and the response was greater (P <0.05) than in water-replete rats (-4 ± 1 mmHg). Finally, as in PVN, candesartan in RVLM slowly decreased BP in water-deprived (-8 ± 1 mmHg; P <0.05) but not in water-replete (-3 ± 1 mmHg) rats. These data suggest that activation of AT1 and glutamate receptors in PVN, as well as of AT1R in RVLM, contributes to BP maintenance during water deprivation.",
keywords = "Angiotensin II, Candesartan, Glutamate, Rostral ventrolateral medulla, Valsartan",
author = "Freeman, {Korrina L.} and Virginia Brooks",
year = "2007",
month = "4",
doi = "10.1152/ajpregu.00623.2006",
language = "English (US)",
volume = "292",
journal = "American Journal of Physiology - Renal Fluid and Electrolyte Physiology",
issn = "1931-857X",
publisher = "American Physiological Society",
number = "4",

}

TY - JOUR

T1 - AT1 and glutamatergic receptors in paraventricular nucleus support blood pressure during water deprivation

AU - Freeman, Korrina L.

AU - Brooks, Virginia

PY - 2007/4

Y1 - 2007/4

N2 - Water deprivation activates sympathoexcitatory neurons in the paraventricular nucleus (PVN); however, the neurotransmitters that mediate this activation are unknown. To test the hypothesis that ANG II and glutamate are involved, effects on blood pressure (BP) of bilateral PVN microinjections of ANG II type 1 receptor (AT1R) antagonists, candesartan and valsartan, or the ionotropic glutamate receptor antagonist, kynurenate, were determined in urethane-anesthetized water-deprived and water-replete male rats. Because PVN may activate sympathetic neurons via the rostral ventrolateral medulla (RVLM) and because PVN disinhibition increases sympathetic activity in part via increased drive of AT1R in the RVLM, candesartan was also bilaterally microinjected into the RVLM. Total blockade of the PVN with bilateral microinjections of muscimol, a GABAA agonist, decreased BP more (P <0.05) in water-deprived (-29 ± 8 mmHg) than in water-replete (-7 ± 2 mmHg) rats, verifying that the PVN is required for BP maintenance during water deprivation. PVN candesartan slowly lowered BP by 7 ± 1 mmHg (P <0.05). In water-replete rats, however, candesartan did not alter BP (1 ± 1 mmHg). Valsartan also produced a slowly developing decrease in arterial pressure (-6 ± 1 mmHg; P <0.05) in water-deprived but not in water-replete (-1 ± 1 mmHg) rats. In water-deprived rats, PVN kynurenate rapidly decreased BP (-19 ± 3 mmHg), and the response was greater (P <0.05) than in water-replete rats (-4 ± 1 mmHg). Finally, as in PVN, candesartan in RVLM slowly decreased BP in water-deprived (-8 ± 1 mmHg; P <0.05) but not in water-replete (-3 ± 1 mmHg) rats. These data suggest that activation of AT1 and glutamate receptors in PVN, as well as of AT1R in RVLM, contributes to BP maintenance during water deprivation.

AB - Water deprivation activates sympathoexcitatory neurons in the paraventricular nucleus (PVN); however, the neurotransmitters that mediate this activation are unknown. To test the hypothesis that ANG II and glutamate are involved, effects on blood pressure (BP) of bilateral PVN microinjections of ANG II type 1 receptor (AT1R) antagonists, candesartan and valsartan, or the ionotropic glutamate receptor antagonist, kynurenate, were determined in urethane-anesthetized water-deprived and water-replete male rats. Because PVN may activate sympathetic neurons via the rostral ventrolateral medulla (RVLM) and because PVN disinhibition increases sympathetic activity in part via increased drive of AT1R in the RVLM, candesartan was also bilaterally microinjected into the RVLM. Total blockade of the PVN with bilateral microinjections of muscimol, a GABAA agonist, decreased BP more (P <0.05) in water-deprived (-29 ± 8 mmHg) than in water-replete (-7 ± 2 mmHg) rats, verifying that the PVN is required for BP maintenance during water deprivation. PVN candesartan slowly lowered BP by 7 ± 1 mmHg (P <0.05). In water-replete rats, however, candesartan did not alter BP (1 ± 1 mmHg). Valsartan also produced a slowly developing decrease in arterial pressure (-6 ± 1 mmHg; P <0.05) in water-deprived but not in water-replete (-1 ± 1 mmHg) rats. In water-deprived rats, PVN kynurenate rapidly decreased BP (-19 ± 3 mmHg), and the response was greater (P <0.05) than in water-replete rats (-4 ± 1 mmHg). Finally, as in PVN, candesartan in RVLM slowly decreased BP in water-deprived (-8 ± 1 mmHg; P <0.05) but not in water-replete (-3 ± 1 mmHg) rats. These data suggest that activation of AT1 and glutamate receptors in PVN, as well as of AT1R in RVLM, contributes to BP maintenance during water deprivation.

KW - Angiotensin II

KW - Candesartan

KW - Glutamate

KW - Rostral ventrolateral medulla

KW - Valsartan

UR - http://www.scopus.com/inward/record.url?scp=34147123055&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34147123055&partnerID=8YFLogxK

U2 - 10.1152/ajpregu.00623.2006

DO - 10.1152/ajpregu.00623.2006

M3 - Article

VL - 292

JO - American Journal of Physiology - Renal Fluid and Electrolyte Physiology

JF - American Journal of Physiology - Renal Fluid and Electrolyte Physiology

SN - 1931-857X

IS - 4

ER -